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PARP抑制剂在卵巢癌患者中的疗效及预后因素

Efficacy and Prognostic Factors for PARP Inhibitors in Patients With Ovarian Cancer.

作者信息

Huang Xuan-Zhang, Jia Han, Xiao Qiong, Li Run-Zhou, Wang Xing-Shuang, Yin Hai-Yan, Zhou Xin

机构信息

Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Department of Surgical Oncology and General Surgery, Ministry of Education, The First Affiliated Hospital of China Medical University, Shenyang, China.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Oncol. 2020 Jun 16;10:958. doi: 10.3389/fonc.2020.00958. eCollection 2020.

Abstract

The prognostic factors for efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer remain unknown. The purpose of this study is to evaluate the efficacy of PARP inhibitors and to explore their prognostic factors in ovarian cancer. PubMed, Embase, and conference databases were searched for relevant prospective clinical trials. The primary outcomes included overall survival (OS), progression-free survival (PFS), and their prognostic factors. Secondary outcomes included PFS2, time to first subsequent therapy (TFST), time to second subsequent therapy (TSST), chemotherapy-free interval (CFI), and their prognostic factors. Hazard ratio (HR) with a 95% confidence interval (CI) was used as an effect measure. PARP inhibitors significantly prolonged PFS in patients with ovarian cancer regardless of their BRCA and HRD status (HR = 0.44, 95% CI = 0.36-0.55). BRCA mutation, HRD-positive status, and sensitivity to platinum represented effective prognostic factors for PFS (P < 0.01 and within-trial interaction HR < 1). Other clinicopathological factors did not predict the benefit of PFS (P > 0.10). Moreover, PARP inhibitors significantly increased PFS2, TFST, TSST, and CFI, with significant BRCA-related differences. However, HRD-related differences could not be evaluated due to the lack of eligible studies. Furthermore, PARP inhibitors did not translate into prolonged OS, although there was a benefit associated with OS (HR = 0.84, 95% CI = 0.70-1.02). PARP inhibitors used as maintenance therapy after first or subsequent line therapy improved OS (HR = 0.77, 95% CI = 0.63-0.93). PARP inhibitors can significantly prolong PFS, PFS2, TFST, TSST, and CFI in ovarian cancer patients. BRCA mutation, HRD-positive status, and sensitivity to platinum are effective prognostic factors for the efficacy of PARP inhibitors. However, despite the PFS improvement, this does not translate into prolonged OS for patients.

摘要

聚(ADP - 核糖)聚合酶(PARP)抑制剂治疗卵巢癌疗效的预后因素尚不清楚。本研究的目的是评估PARP抑制剂的疗效,并探索其在卵巢癌中的预后因素。检索了PubMed、Embase和会议数据库以查找相关的前瞻性临床试验。主要结局包括总生存期(OS)、无进展生存期(PFS)及其预后因素。次要结局包括PFS2、首次后续治疗时间(TFST)、第二次后续治疗时间(TSST)、无化疗间期(CFI)及其预后因素。采用具有95%置信区间(CI)的风险比(HR)作为效应量度。无论BRCA和HRD状态如何,PARP抑制剂均能显著延长卵巢癌患者的PFS(HR = 0.44,95% CI = 0.36 - 0.55)。BRCA突变、HRD阳性状态和对铂类的敏感性是PFS的有效预后因素(P < 0.01且试验内交互作用HR < 1)。其他临床病理因素不能预测PFS的获益(P > 0.10)。此外,PARP抑制剂显著增加了PFS2、TFST、TSST和CFI,存在显著的BRCA相关差异。然而,由于缺乏符合条件的研究,无法评估HRD相关差异。此外,尽管OS有获益趋势(HR = 0.84,95% CI = 0.70 - 1.02),但PARP抑制剂并未转化为OS的延长。PARP抑制剂作为一线或后续治疗后的维持治疗可改善OS(HR = 0.77,95% CI = 0.63 - 0.93)。PARP抑制剂可显著延长卵巢癌患者的PFS、PFS2、TFST、TSST和CFI。BRCA突变、HRD阳性状态和对铂类的敏感性是PARP抑制剂疗效的有效预后因素。然而,尽管PFS有所改善,但这并未转化为患者OS的延长。

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